Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001885828 | SCV002144287 | uncertain significance | Brugada syndrome | 2021-03-01 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with CACNA2D1-related conditions. This sequence change replaces alanine with valine at codon 907 of the CACNA2D1 protein (p.Ala907Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002425160 | SCV002743593 | uncertain significance | Cardiovascular phenotype | 2020-07-02 | criteria provided, single submitter | clinical testing | The p.A907V variant (also known as c.2720C>T), located in coding exon 33 of the CACNA2D1 gene, results from a C to T substitution at nucleotide position 2720. The alanine at codon 907 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |